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https://www.readbyqxmd.com/read/29134279/dietary-k-and-cl-independently-regulate-basolateral-conductance-in-principal-and-intercalated-cells-of-the-collecting-duct
#1
Viktor N Tomilin, Oleg Zaika, Arohan R Subramanya, Oleh Pochynyuk
The renal collecting duct contains two distinct cell types, principal and intercalated cells, expressing potassium Kir4.1/5.1 (KCNJ10/16) and chloride ClC-K2 (ClC-Kb in humans) channels on their basolateral membrane, respectively. Both channels are thought to play important roles in controlling systemic water-electrolyte balance and blood pressure. However, little is known about mechanisms regulating activity of Kir4.1/5.1 and ClC-K2/b. Here, we employed patch clamp analysis at the single channel and whole cell levels in freshly isolated mouse collecting ducts to investigate regulation of Kir4...
November 13, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29122955/dnpep-is-not-the-only-peptidase-that-produces-spak-fragments-in-kidney
#2
Rainelli Koumangoye, Eric Delpire
SPAK (STE20/SPS1-related proline/alanine-rich kinase) regulates Na(+) and Cl(-) reabsorption in the distal convoluted tubule, and possibly in the thick ascending limb of Henle. This kinase phosphorylates and activates the apical Na-Cl cotransporter in the DCT. Western blot analysis reveals that SPAK in kidney exists as a full-length protein as well as shorter fragments that might affect NKCC2 function in the TAL. Recently, we showed that kidney lysates exerts proteolytic activity towards SPAK, resulting in the formation of multiple SPAK fragments with possible inhibitory effects on the kinase...
November 2017: Physiological Reports
https://www.readbyqxmd.com/read/29101099/insulin-regulates-multiple-signaling-pathways-leading-to-monocyte-macrophage-chemotaxis-into-the-wound-tissue
#3
Yan Liu, Sandeep Dhall, Anthony Castro, Alex Chan, Raquelle Alamat, Manuela Martins-Green
Wound healing is a complex process that involves sequential phases that overlap in time and space and affect each other dynamically at the gene and protein levels. We previously showed that insulin accelerates wound healing by stimulating faster and regenerative healing. One of the processes that insulin stimulates is an increase in monocyte/macrophage chemotaxis. In this study, we performed experiments in vivo and in vitro to elucidate the signaling transduction pathways that are involved in insulin-induced monocyte/macrophage chemotaxis...
November 3, 2017: Biology Open
https://www.readbyqxmd.com/read/29094747/calibration-and-evaluation-of-puf-pas-sampling-rates-across-the-global-atmospheric-passive-sampling-gaps-network
#4
Nicholas J Herkert, Scott N Spak, Austen Smith, Jasmin K Schuster, Tom Harner, Andres Martinez, Keri C Hornbuckle
Passive air samplers equipped with polyurethane foam (PUF-PAS) are frequently used to measure persistent organic pollutants (POPs) in ambient air. Here we present and evaluate a method to determine sampling rates (RS), and the effective sampling volume (Veff), for gas-phase chemical compounds captured by a PUF-PAS sampler deployed anywhere in the world. The method uses a mathematical model that requires only publicly available hourly meteorological data, physical-chemical properties of the target compound, and the deployment dates...
November 2, 2017: Environmental Science. Processes & Impacts
https://www.readbyqxmd.com/read/29092909/n-ethylmaleimide-increases-kcc2-activity-by-modulating-transporter-phosphorylation
#5
Leslie C Conway, Ross A Cardarelli, Yvonne E Moore, Karen Jones, Lisa J McWilliams, David J Baker, Matthew P Burnham, Roland W Bürli, Qi Wang, Nicholas J Brandon, Stephen J Moss, Tarek Z Deeb
The K+/Cl- co-transporter (KCC2) is selectively expressed in the adult nervous system, and allows neurons to maintain low intracellular Cl- levels. Thus, KCC2 activity is an essential prerequisite for fast hyperpolarizing synaptic inhibition mediated by type A γ-aminobutyric acid receptors (GABAA), which are Cl- permeable, ligand-gated ion channels. Consistent with this, deficits in the activity of KCC2 lead to epilepsy, and are also implicated in neurodevelopmental disorders, neuropathic pain, and schizophrenia...
November 1, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29066461/inactivation-of-spak-kinase-reduces-body-weight-gain-in-mice-fed-a-high-fat-diet-by-improving-energy-expenditure-and-insulin-sensitivity
#6
Ivan Torre-Villalvazo, Luz Graciela Cervantes-Perez, Lilia G Noriega, Jose V Jimenez, Norma Uribe, Maria Chavez-Canales, Claudia Tovar-Palacio, Braulio A Marfil-Garza, Nimbe Torres, Norma A Bobadilla, Armando R Tovar, Gerardo Gamba
The STE20/SPS1-related proline-alanine-rich protein kinase (SPAK) controls the activity of the electroneutral cation-chloride cotransporters (SLC12 family) and thus physiological processes such as modulation of cell volume, intracellular chloride concentration [Cl-]i and transepithelial salt transport. Modulation of SPAK kinase activity may have an impact on hypertension and obesity as STK39, the gene encoding SPAK has been suggested as a hypertension and obesity susceptibility gene. In fact, the absence of SPAK activity in mice in which the activating threonine in the T-loop was substituted by alanine (SPAK-KI mice) is associated with decreased blood pressure; however its consequences in metabolism have not been explored...
October 24, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29050631/drug-coated-balloon-treatment-for-femoropopliteal-artery-disease-the-in-pact-global-study-de-novo-in-stent-restenosis-imaging%C3%A2-cohort
#7
Marianne Brodmann, Koen Keirse, Dierk Scheinert, Lubomir Spak, Michael R Jaff, Randy Schmahl, Pei Li, Thomas Zeller
OBJECTIVES: This study sought to evaluate the safety and effectiveness of a paclitaxel-coated drug-coated balloon (DCB) for the treatment of patients with de novo in-stent restenosis (ISR). BACKGROUND: Treatment of patients with ISR remains a challenge. Current strategies are plagued by high rates of recurrent restenosis and need for reintervention. The best intervention for ISR remains to be elucidated. METHODS: The IN.PACT Global study is an independently adjudicated multicenter, prospective, single-arm study that enrolled 1,535 subjects with symptomatic atherosclerotic disease of the superficial femoral and/or popliteal arteries, including de novo ISR lesions...
October 23, 2017: JACC. Cardiovascular Interventions
https://www.readbyqxmd.com/read/28888841/implications-of-the-n-terminal-heterogeneity-for-the-neuronal-k-cl-cotransporter-kcc2-function
#8
Marika Markkanen, Anastasia Ludwig, Stanislav Khirug, Evgeny Pryazhnikov, Shetal Soni, Leonard Khiroug, Eric Delpire, Claudio Rivera, Matti S Airaksinen, Pavel Uvarov
The neuron-specific K-Cl cotransporter KCC2 maintains the low intracellular chloride concentration required for the fast hyperpolarizing responses of the inhibitory neurotransmitters γ-aminobutyric acid (GABA) and glycine. The two KCC2 isoforms, KCC2a and KCC2b differ by their N-termini as a result of alternative promoter usage. Whereas the role of KCC2b in mediating the chloride transport is unequivocal, the physiological role of KCC2a in neurons has remained obscure. We show that KCC2a isoform can decrease the intracellular chloride concentration in cultured neurons and attenuate calcium responses evoked by application of the GABAA receptor agonist muscimol...
November 15, 2017: Brain Research
https://www.readbyqxmd.com/read/28877076/disruption-of-the-with-no-lysine-kinase-ste20-proline-alanine-rich-kinase-pathway-reduces-the-hypertension-induced-by-angiotensin-ii
#9
Luz G Cervantes-Perez, Maria Castaneda-Bueno, Jose V Jimenez, Norma Vazquez, Lorena Rojas-Vega, Dario R Alessi, Norma A Bobadilla, Gerardo Gamba
OBJECTIVE: The hypertensive effect of angiotensin II (AngII), a peptide hormone, is dependent on its intrarenal actions and the activation of the renal Na-Cl cotransporter (NCC), by AngII requires integrity of the with no lysine kinase/STE20-proline alanine-rich kinase (WNK/SPAK) signaling pathway. Here, we analyzed if the integrity of the WNK/SPAK pathway is required for AngII infusion to induce arterial hypertension. METHODS: We tested the effect of AngII or aldosterone administration on the blood pressure and on pNCC/NCC ratio in SPAK knock-in mice in which the kinase and thus NCC cannot be activated by WNK kinases...
September 14, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28864211/effects-of-spak-on-vascular-reactivity-and-nitric-oxide-production-in-endotoxemic-mice
#10
Chih-Chin Shih, Lin-Pin Hsu, Mei-Hui Liao, Sung-Sen Yang, Shung-Tai Ho, Chin-Chen Wu
Vasoplegia impedes therapeutic interventions to restore vascular tone, leading to severe hypotension, poor tissue perfusion, and multiple organ failure in septic shock. High levels of circulating nitric oxide (NO) play a crucial role in endotoxin-induced vascular hyporeactivity. Proinflammatory cytokines have been implicated in the induction of inducible NO synthase and overproduction of NO. Anti-inflammatory therapy can diminish NO formation and improve vascular hyporeactivity in septic shock. STE20/SPS1-realted proline/alanine-rich kinase (SPAK) has been reported to activate mitogen-activated protein kinase and contribute to intestinal inflammation...
November 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28818393/the-modulation-of-the-phosphorylation-status-of-nkcc1-in-organ-cultured-bovine-lenses-implications-for-the-regulation-of-fiber-cell-and-overall-lens-volume
#11
Irene Vorontsova, Paul J Donaldson, Zhiying Kong, Chiharu Wickremesinghe, Leo Lam, Julie C Lim
In previous work, we have shown the Sodium/Potassium/2 Chloride Cotransporter (NKCC1) to be a key effector of lens fiber cell volume regulation. Since others have shown that the activity of NKCC1 is regulated via its phosphorylation status, the purpose of this study was to investigate whether NKCC1 phosphorylation can be modulated in organ cultured bovine lenses, and to see how this relates to changes in lens wet weight. Western blotting was first used to confirm the expression of NKCC1, phosphorylated NKCC1 (NKCC1-P) and the regulatory kinases WNK/SPAK and phosphatases PP1/PP2A in bovine lenses at the protein level...
August 14, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28743496/wnk4-is-indispensable-for-the-pathogenesis-of-pseudohypoaldosteronism-type-ii-caused-by-mutant-klhl3
#12
Koichiro Susa, Eisei Sohara, Daiei Takahashi, Tomokazu Okado, Tatemitsu Rai, Shinichi Uchida
WNK-OSR1/SPAK-NCC signaling cascade is important for regulating salt balance and blood pressure. Activation of WNK-OSR1/SPAK-NaCl cotransporter (NCC) cascade increases sodium reabsorption in the kidney, leading to pseudohypoaldosteronism type II (PHA II) characterized by salt-sensitive hypertension and hyperkalemia. It has been previously demonstrated that the amount of phosphorylated and total NCC markedly decreased in WNK4(-/-) mice, indicating that WNK4 plays a major role for activation of OSR1/SPAK-NCC signaling...
September 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28710266/specificity-of-subtilin-mediated-activation-of-histidine-kinase-spak
#13
Christoph Geiger, Tobias Spieß, Sophie Marianne Korn, Peter Kötter, Karl-Dieter Entian
Autoinduction via two-component systems is a widespread regulatory mechanism that senses environmental and metabolic changes. Although the lantibiotics nisin and subtilin are closely related and share the same lanthionine ring structure, they autoinduce their biosynthesis in a highly specific manner. Subtilin can only activate the two-component system SpaRK of Bacillus subtilis, whereas nisin activates solely the two-component system NisRK of Lactococcus lactis To identify components that determine the specificity of subtilin autoinduction, several variants of the respective lantibiotic were analyzed for their autoinduction capacity...
July 14, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28692063/inflammation-dependent-cerebrospinal-fluid-hypersecretion-by-the-choroid-plexus-epithelium-in-posthemorrhagic-hydrocephalus
#14
Jason K Karimy, Jinwei Zhang, David B Kurland, Brianna Carusillo Theriault, Daniel Duran, Jesse A Stokum, Charuta Gavankar Furey, Xu Zhou, M Shahid Mansuri, Julio Montejo, Alberto Vera, Michael L DiLuna, Eric Delpire, Seth L Alper, Murat Gunel, Volodymyr Gerzanich, Ruslan Medzhitov, J Marc Simard, Kristopher T Kahle
The choroid plexus epithelium (CPE) secretes higher volumes of fluid (cerebrospinal fluid, CSF) than any other epithelium and simultaneously functions as the blood-CSF barrier to gate immune cell entry into the central nervous system. Posthemorrhagic hydrocephalus (PHH), an expansion of the cerebral ventricles due to CSF accumulation following intraventricular hemorrhage (IVH), is a common disease usually treated by suboptimal CSF shunting techniques. PHH is classically attributed to primary impairments in CSF reabsorption, but little experimental evidence supports this concept...
August 2017: Nature Medicine
https://www.readbyqxmd.com/read/28679296/pharmacological-targeting-of-spak-kinase-in-disorders-of-impaired-epithelial-transport
#15
REVIEW
Jinwei Zhang, Jason K Karimy, Eric Delpire, Kristopher T Kahle
The mammalian SPS1-related proline/alanine-rich serine-threonine kinase SPAK (STK39) modulates ion transport across and between epithelial cells in response to environmental stimuli such osmotic stress and inflammation. Research over the last decade has established a central role for SPAK in the regulation of ion and water transport in the distal nephron, colonic crypts, and pancreatic ducts, and has implicated deregulated SPAK signaling in NaCl-sensitive hypertension, ulcerative colitis and Crohn's disease, and cystic fibrosis...
August 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28656378/comparative-transcriptomic-analysis-identifies-evolutionarily-conserved-gene-products-in-the-vertebrate-renal-distal-convoluted-tubule
#16
REVIEW
Yuya Sugano, Chiara Cianciolo Cosentino, Dominique Loffing-Cueni, Stephan C F Neuhauss, Johannes Loffing
Understanding the molecular basis of the complex regulatory networks controlling renal ion transports is of major physiological and clinical importance. In this study, we aimed to identify evolutionarily conserved critical players in the function of the renal distal convoluted tubule (DCT) by a comparative transcriptomic approach. We generated a transgenic zebrafish line with expression of the red fluorescent mCherry protein under the control of the zebrafish DCT-specific promoter of the thiazide-sensitive NaCl cotransporter (NCC)...
August 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28585868/long-term-effects-of-internet-delivered-cognitive-behavioral-therapy-for-depression-in-primary-care-the-prim-net-controlled-trial
#17
Maria C M Eriksson, Marie Kivi, Dominique Hange, Eva-Lisa Petersson, Nashmil Ariai, Per Häggblad, Hans Ågren, Fredrik Spak, Ulf Lindblad, Boo Johansson, Cecilia Björkelund
OBJECTIVE: Internet-delivered cognitive behavioral therapy (ICBT) is recommended as an efficient treatment alternative for depression in primary care. However, only few previous studies have been conducted at primary care centers (PCCs). We evaluated long-term effects of ICBT treatment for depression compared to treatment as usual (TAU) in primary care settings. DESIGN: Randomized controlled trial. SETTING: Patients were enrolled at16 PCCs in south-west Sweden...
June 2017: Scandinavian Journal of Primary Health Care
https://www.readbyqxmd.com/read/28567665/severe-hyperkalemia-is-rescued-by-low-potassium-diet-in-renal-%C3%AE-enac-deficient-mice
#18
Emilie Boscardin, Romain Perrier, Chloé Sergi, Marc Maillard, Johannes Loffing, Dominique Loffing-Cueni, Robert Koesters, Bernard Claude Rossier, Edith Hummler
In adulthood, an induced nephron-specific deficiency of αENaC (Scnn1a) resulted in pseudohypoaldosteronism type 1 (PHA-1) with sodium loss, hyperkalemia, and metabolic acidosis that is rescued through high-sodium/low-potassium (HNa(+)/LK(+)) diet. In the present study, we addressed whether renal βENaC expression is required for sodium and potassium balance or can be compensated by remaining (α and γ) ENaC subunits using adult nephron-specific knockout (Scnn1b(Pax8/LC1)) mice. Upon induction, these mice present a severe PHA-1 phenotype with weight loss, hyperkalemia, and dehydration, but unlike the Scnn1a(Pax8/LC1) mice without persistent salt wasting...
May 31, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28566208/development-of-wnk-signaling-inhibitors-as-a-new-class-of-antihypertensive-drugs
#19
Mari Ishigami-Yuasa, Yuko Watanabe, Takayasu Mori, Hiroyuki Masuno, Shinya Fujii, Eriko Kikuchi, Shinichi Uchida, Hiroyuki Kagechika
Pseudohypoaldosteronism type II (PHAII) is characterized by hyperkalemia and hypertension despite a normal glomerular filtration rate. Abnormal activation of the signal cascade of with-no-lysine kinase (WNK) with OSR1 (oxidative stress-responsive kinase 1)/SPAK (STE20/SPS1-related proline/alanine-rich kinase) and NCC (NaCl cotransporter) results in characteristic salt-sensitive hypertension. Thus, inhibitors of the WNK-OSR1/SPAK-NCC cascade are candidates for a new class of antihypertensive drugs. In this study, we developed novel inhibitors of this signal cascade from the 9-aminoacridine lead compound 1, one of the hit compounds obtained by screening our chemical library for WNK-SPAK binding inhibitors...
July 15, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28560800/emerging-targets-of-diuretic-therapy
#20
REVIEW
C-J Cheng, A R Rodan, C-L Huang
Diuretics are commonly prescribed for treatment in patients with hypertension, edema, or heart failure. Studies on hypertensive and salt-losing disorders and on urea transporters have contributed to better understanding of mechanisms of renal salt and water reabsorption and their regulation. Proteins involved in the regulatory pathways are emerging targets for diuretic and aquaretic therapy. Integrative high-throughput screening, protein structure analysis, and chemical modification have identified promising agents for preclinical testing in animals...
September 2017: Clinical Pharmacology and Therapeutics
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